RATIONALE: High doses of testosterone may be effective in killing prostate cancer cells that
no longer respond to hormone therapy.
PURPOSE: Phase I trial to study the effectiveness of testosterone in treating patients who
have progressive prostate cancer that no longer responds to hormone therapy.
- Determine the safety and maximum tolerated dose of exogenously administered
testosterone in patients with progressive androgen-independent prostate cancer who have
been in castrate state either surgically or pharmacologically for a minimum of 1 year.
- Assess the changes in expression of androgen receptor and other receptors in human
biopsy specimens or circulating tumor cells before and after this treatment in this
OUTLINE: This is a dose-escalation study.
Patients receive testosterone via an enhanced absorption transdermal system continuously for
28 days. The transdermal patches are changed daily.
Cohorts of 3-6 patients receive a fixed daily dose of testosterone with escalating duration
of exposure until the maximum tolerated dose (MTD) is determined. The MTD is defined as the
dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicities.
Patients are followed at day 1 and at weeks 2 and 4.
PROJECTED ACCRUAL: A total of 3-18 patients will be accrued for this study.
- Histologically confirmed androgen independent metastatic prostate cancer
- Progressive disease manifested by either:
- New osseous lesions by bone scan or a greater than 25% increase in
bidimensionally measurable soft tissue disease or the appearance of new sites of
disease by MRI or CT scan OR
- Minimum of 3 rising PSA values from baseline that are obtained 1 week or more
apart, or 2 rising PSA values more than 1 month apart, where the percentage
increase over the range of values is at least 25%
- Castrate state by orchiectomy or gonadotropin-releasing hormone analogues for minimum
of 1 year
- Testosterone no greater than 30 ng/mL
- Measurable disease
- Metastatic disease by bone scan, MRI, or CT scan
- Rising PSA values
- If receiving antiandrogen therapy, must have shown progressive disease off treatment
- No active CNS or epidural tumor
- 18 and over
- Karnofsky 60-100%
- Not specified
- WBC at least 3,500/mm^3
- Platelet count greater than 100,000/mm^3
- Bilirubin less than 2.0 mg/dL
- SGOT less than 3 times upper limit of normal
- PTT less than 14 seconds
- Creatinine less than 2.0 mg/dL OR
- Creatinine clearance greater than 60 mL/min
- No New York Heart Association class III or IV cardiac disease
- No severe debilitating pulmonary disease
- No infection requiring IV antibiotics
- No other severe medical problems that would increase risk for toxicity
PRIOR CONCURRENT THERAPY:
- Recovered from prior biologic therapy
- No concurrent immunotherapy
- Recovered from prior chemotherapy
- No concurrent chemotherapy
- See Disease Characteristics
- If no prior orchiectomy, must continue on gonadotropin-releasing hormone analogs to
maintain castrate levels of testosterone
- No concurrent finasteride
- No other concurrent hormonal therapy
- Recovered from prior radiotherapy
- No concurrent radiotherapy to an indicator lesion
- See Disease Characteristics
- Recovered from prior surgery
- No concurrent surgery on only measurable lesion
- At least 4 weeks since other prior investigational anticancer drugs and recovered
- No other concurrent investigational anticancer agents